PROJECT SUMMARY TRD 3: RAMAN SPECTROSCOPY AND IMAGING Investigators: R.R. Dasari (3.1) [co-lead]; I. Barman (3.2); C.L. Evans (3.3) [co-lead] Raman technologies offer the ability to detect, quantify, and visualize molecular species with high sensitivity and high resolution via their unique vibrational fingerprints, enabling a host of biomedical applications ranging from bench to the bedside. The LBRC has been a leader in Raman technology development with contributions such as: blood glucose sensing toolkits, chemometric algorithms, and clinical Raman spectroscopy systems. In this next cycle, the LBRC pushes technologies in three exciting areas: developing a high-speed multimodal confocal Raman and phase microscopy with enhanced resolution to enhance cellular mechanobiology studies (Aim 3.1), developing technologies for probing cellular nanomechanics and the accompanying biological responses (Aim 3.2), and developing a portable, robust clinical coherent Raman imaging system for the assessment of melanoma and other diseases of the skin in vivo (Aim 3.3). The collaboration with Dr. Kato investigates how sickle red cells aging affects their mechanical properties using Raman imaging of long term glycemic markers to quantify cell age and phase imaging of membrane fluctuations to quantify cell mechanics (CP2). The collaboration with Dr. Raman seeks to dissect organ-specific differences in metastatic breast cancer by determining microenvironment induced biophysical and molecular adaptations (CP5). This collaborative effort will offer mechanistic insights into metastasis organotropism, a critical step towards discovering optimal treatment strategies for specific metastatic lesions to improve overall survival. The ongoing collaborative project with Dr. Fisher will translate current findings on the oncogenic nature of the natural pigment pheomelanin in animal models to human studies focused on the identification and therapy of amelanotic melanomas (CP6).